Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease

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Authors: Dereje A Negatu ; Sung Jae Shin ; Su-Young Kim ; Byung Woo Jhun ; Véronique Dartois ; Thomas Dick

MeSH: Administration, Oral ; Anti-Bacterial Agents* / administration & dosage ; Anti-Bacterial Agents* / therapeutic use ; Humans ; Lung Diseases / drug therapy ; Lung Diseases / microbiology ; Microbial Sensitivity Tests ; Mycobacterium avium Complex* / drug effects ; Mycobacterium avium-intracellulare Infection* / drug therapy ; Mycobacterium avium-intracellulare Infection* / microbiology ; beta-Lactams* / administration & dosage ; beta-Lactams* / therapeutic use

Keywords: Mycobacterium avium complex ; amoxicillin ; cefuroxime ; nontuberculous mycobacteria ; sulopenem ; synergy ; target attainment ; tebipenem ; β-lactam

Abstract: Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.